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Design, synthesis, and evaluation of pyranochromene derivatives as membrane targeting antibacterials against Gram-positive bacteria.
Wang, Yinhu; Miao, Guoqing; Wang, Shuo; Zhou, Fen.
Afiliación
  • Wang Y; State Key Laboratory for Macromolecule Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China. Electronic address: wangyinhuabc@126.com.
  • Miao G; State Key Laboratory for Macromolecule Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China.
  • Wang S; State Key Laboratory for Macromolecule Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences and Food Engineering, Liaocheng University, Liaocheng 252059, China.
  • Zhou F; Department of Pharmacy, Liaocheng People's Hospital, Liaocheng, China. Electronic address: fenzhouwyh@163.com.
Bioorg Med Chem Lett ; 113: 129949, 2024 Nov 15.
Article en En | MEDLINE | ID: mdl-39243868
ABSTRACT
The rapid growth of bacterial resistance has created obstacles for the effective treatment with conventional antibiotics, simultaneously posing a major threat to public health. In this study, a class of novel amphipathic pyranochromene derivatives were designed and synthesized by mimicking the amphiphilic characteristics of AMPs. Bioactivity screening identified a lead compound 5a with broad-spectrum antibacterial activity against Gram-positive stains (MICs = 1-4 µg/mL) and low hemolytic toxicity (HC50 = 111.6 µg/mL). Additionally, compound 5a displayed rapid bactericidal action, and was unlikely to induce bacterial resistance. Mechanistic investigation further demonstrated that compound 5a was able to disrupt the transmembrane potential and increased membrane permeability of S. aureus, which in turn causes leakage of cell contents such as DNA and proteins, ultimately leading to bacterial death. These findings indicated that compound 5a is a promising lead to combat bacterial infection caused by Gram-positive bacteria.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzopiranos / Diseño de Fármacos / Pruebas de Sensibilidad Microbiana / Bacterias Grampositivas / Antibacterianos Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzopiranos / Diseño de Fármacos / Pruebas de Sensibilidad Microbiana / Bacterias Grampositivas / Antibacterianos Límite: Humans Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido